THE HEPATITIS-B VIRUS MHBS(T167) PROTEIN IS A PLEIOTROPIC TRANSACTIVATOR MEDIATING ITS EFFECT VIA UBIQUITOUS CELLULAR TRANSCRIPTION FACTORS

C-terminally truncated surface proteins of hepatitis B virus (HBV) are frequently translated from genomically integrated viral sequences, Th ey may be relevant for hepatocarcinogenesis by stimulating gene expres sion. First, we examined the transactivating potential of middle hepat itis B surface protein truncated at amino acid (aa) position 167 (MHBs (1167)) on the HBV regulatory element, In transient cotransfection ass ays using Chang liver or HepG2 cell lines and chloramphenicol acetyltr ansferase (CAT) reporter constructs only the HBV enhancer I, but no ot her HBV regulatory elements like the X promoter, the S1 or S2 promoter or the enhancer II/core promoter could be stimulated by MHBs(1167). S ince there is no evidence for a direct interaction of MHBs(1167) With DNA, we subsequently analysed whether cellular transcription factors w ere involved in mediating transactivation. This was tested both with i solated transcription-factor-binding sites and in the natural context of viral and cellular promoter elements. Deletion analysis and electro phoretic mobility shift assays revealed that Sp1, AP1 and NF-kappa B c an mediate transactivation by MHBs(1167). NO involvement of CREB, NF1 or the liver-specific factor C/EBP was found. These data indicate that MHBs(1167) is a pleiotropic, non-liver-specific transactivator which exerts its effect via ubiquitous cellular transcription factors that a re also involved in the regulation of expression of cellular genes rel evant for proliferation and inflammation.